AXIN2 variants, tooth agenesis, and cancer risk: a systematic review

ABSTRACT

Background

Variants in the Axis Inhibition Protein 2 (AXIN2) have been associated with tooth agenesis, a congenital condition characterized by missing teeth, and an increased risk of various cancers. Studies suggest that individuals with AXIN2 variants may exhibit both dental anomalies and a predisposition to malignancies, particularly colorectal cancer. This raises the possibility that tooth agenesis could serve as an early clinical marker for identifying individuals at higher cancer risk.

Method

A systematic review was conducted using data from 20 studies with 91 patients carrying 34 unique AXIN2 variants. The number and pattern of missing teeth, as well as the occurrence of cancer types, were evaluated. The genotypic location of AXIN2 variants was also assessed for clinical significance.

Results

Most AXIN2 variants were located within the SMAD3 domain. Patients with both tooth agenesis and cancer were more common than those with either condition alone. Among the mutation types, nonsense AXIN2 variants were associated with the most severe tooth agenesis phenotype, averaging 12.9 missing teeth. Second premolars were most frequently missing, and maxillary central incisors were least affected. Regarding cancer, colorectal cancer and polyps were the most common malignancies observed in both sexes, followed by breast and ovarian cancer in females and skin cancer in males.

Conclusion

Tooth agenesis, especially in individuals with AXIN2 variants affecting the SMAD3 domain, may serve as a clinical marker for identifying individuals at increased cancer risk. Recognizing congenital missing teeth in patients with AXIN2 mutations can aid in early cancer screening, improving early detection and outcomes through timely interventions and surveillance.